Can misfolded proteins be beneficial? The HAMLET case

  title={Can misfolded proteins be beneficial? The HAMLET case},
  author={Jenny Pettersson-Kastberg and Sonja Aits and Lotta Gustafsson and Anki Mossberg and Petter Storm and Maria Trulsson and Filip Persson and K. Hun Mok and Catharina Svanborg},
  journal={Annals of Medicine},
  pages={162 - 176}
By changing the three-dimensional structure, a protein can attain new functions, distinct from those of the native protein. Amyloid-forming proteins are one example, in which conformational change may lead to fibril formation and, in many cases, neurodegenerative disease. We have proposed that partial unfolding provides a mechanism to generate new and useful functional variants from a given polypeptide chain. Here we present HAMLET (Human Alpha-lactalbumin Made LEthal to Tumor cells) as an… 
Protein–fatty acid complexes: biochemistry, biophysics and function
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HAMLET: functional properties and therapeutic potential.
Human α-lactalbumin made lethal to tumor cells (HAMLET) is the first member in a new family of protein-lipid complexes that kills tumor cells with high selectivity and limits the progression of human glioblastomas, with no evidence of toxicity for normal brain or bladder tissue.
The structural intolerance of the PrP α-fold for polar substitution of the helix-3 methionines
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Structure and function of human α‐lactalbumin made lethal to tumor cells (HAMLET)‐type complexes
The gain of new, beneficial function upon partial protein unfolding and fatty acid binding is a remarkable phenomenon, and may reflect a significant generic route of functional diversification of proteins via varying their conformational states and associated ligands.
Alternatively folded proteins with unexpected beneficial functions.
The cellular targets that appear to be strongly correlated with tumour cell death are introduced in the present article.
Lipids as Tumoricidal Components of Human α-Lactalbumin Made Lethal to Tumor Cells (HAMLET)
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Bioactivity of α-Lactalbumin Related to its Interaction with Fatty Acids: A Review
The proposed functions for α-LA open new perspectives for its use as a potential ingredient to be added in functional foods or in nutraceutical products.
Structural and mechanistic insights into the yeast disaggregase Hsp104
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Protein misfolding, functional amyloid, and human disease.
The relative importance of the common main-chain and side-chain interactions in determining the propensities of proteins to aggregate is discussed and some of the evidence that the oligomeric fibril precursors are the primary origins of pathological behavior is described.
The structural basis of protein folding and its links with human disease.
  • C. Dobson
  • Biology
    Philosophical transactions of the Royal Society of London. Series B, Biological sciences
  • 2001
Evidence is accumulating that the formation of the highly organized amyloid aggregates is a generic property of polypeptides, and not simply a feature of the few proteins associated with recognized pathological conditions.
Conformational Prerequisites for α-Lactalbumin Fibrillation†
Bovine α-lactalbumin, a small acidic Ca2+-binding milk protein, formed amyloid fibrils at low pH, where it adopted the classical molten globule-like conformation. Fibrillation was accompanied by a
HAMLET, protein folding, and tumor cell death.
Conversion of a-lactalbumin to a protein inducing apoptosis
It is proposed that this single amino acid polypeptide chain may perform vastly different biological functions depending on its folding state and the in vivo environment.
Conversion of alpha-lactalbumin to a protein inducing apoptosis.
It is proposed that this single amino acid polypeptide chain may perform vastly different biological functions depending on its folding state and the in vivo environment.
Formation of amyloid fibers triggered by phosphatidylserine-containing membranes.
Protein misfolding has been shown to be the direct cause of a number of highly devastating diseases such as Alzheimer's disease, Parkinson's disease, and Creutzfeldt-Jacob syndrome, affecting the
Functional Amyloid Formation within Mammalian Tissue
The discovery of an unprecedented functional mammalian amyloid structure generated by the protein Pmel17 is reported, demonstrating thatAmyloid is a fundamental nonpathological protein fold utilized by organisms from bacteria to humans and mitigating the toxicity associated with melanin formation.
Molecular basis for amyloid fibril formation and stability.
The molecular structure of the amyloid fibril has remained elusive because of the difficulty of growing well diffracting crystals, but by using a sequence-designed polypeptide, these crystals diffract to high resolution by electron and x-ray diffraction, enabling the structure to be determined.